Proviral Insertion in Murine Lymphomas 2 Promotes Inflammation and Inhibits Osteogenic Differentiation of Periodontal Ligament Cells via Regulating AMPK and NF-?B Signalings

Periodontitis, a chronic oral inflammatory disease, induces progressive damage to periodontal ligament and leads to tooth loss. Proviral insertion in murine lymphomas 2 (PIM2) promotes activation of NF-KB signaling, and functions as negative regulator of osteoblastogenesis. However, the role of PIM2 in periodontitis remains elusive. Firstly, cell model of periodontitis was established through incubating human periodontal ligament cells (PDLCs) with lipopolysaccharide. Lipopolysaccharide treatment decreased cell viability of PDLCs, promoted the cell apoptosis and enhanced the production of TNF-alpha, IL-8, and IL-6. Secondly, PIM2 expression was up-regulated in gingival tissues of patients with chronic periodontitis and lipopolysaccharide-treated PDLCs. Knockdown of PIM2 enhanced cell viability of lipopolysaccharide-treated PDLCs, and suppressed the cell apoptosis. Moreover, silence of PIM2 attenuated lipopolysaccharide-induced increase of TNF-alpha, IL-8, and IL-6 in PDLCs. Thirdly, the downregulated protein expression of collagen type I alpha 1 (COL1A1), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2) was increased by knockdown of PIM2 in lipopolysaccharide-treated PDLCs was. Lastly, interference of PIM2 up-regulated phosphorylation of AMP-activated protein kinase (AMPK), while down-regulated phosphorylation of p65 in lipopolysaccharide-treated PDLCs. In conclusion, knockdown of PIM2 exerted anti-apoptotic and anti-inflammatory effects against lipopolysaccharide-treated PDLCs, promoted the osteogenic differentiation through activation of AMPK signaling and inactivation of NF-KB signaling.